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Adeno-associated virus enhances wild-type and oncolytic adenovirus spread

Eduardo Laborda1, Cristina Puig-Saus, Manel Cascalló

  • 11 Translational Research Laboratory, IDIBELL-Institut Català d'Oncologia , L'Hospitalet de Llobregat, 08907 Barcelona, Spain .

Human Gene Therapy Methods
|September 12, 2013
PubMed

Insights

Adeno-associated virus (AAV) contamination in adenovirus (Ad) stocks can accelerate Ad release and cell death. Coinfection enhances Ad-mediated cytotoxicity and improves antitumor activity in preclinical models, impacting Ad virotherapy.

Area of Science:

  • Virology
  • Oncolytic Virotherapy

Background:

  • Adenovirus (Ad) stocks are often contaminated with adeno-associated viruses (AAV), typically unnoticed.
  • This contamination is linked to reduced Ad yields during large-scale production and requires routine detection.

Purpose of the Study:

  • To investigate the effects of AAV coinfection on Ad propagation and efficacy.
  • To evaluate the impact of AAV coinfection on Ad-mediated cytotoxicity and antitumor activity in vivo.

Main Methods:

  • Coinfection of cell lines with Ad (wild type 5 or oncolytic) and AAV.
  • Analysis of Ad plaque phenotype, release kinetics, and cell viability.
  • Assessment of antitumor activity and survival in xenograft tumor models following intratumoral coinjection of Ad and AAV.

Main Results:

  • AAV coinfection with Ad resulted in a large-plaque phenotype and accelerated Ad release from infected cells.
  • Ad yields decreased in two of three cell lines tested, but coinfection enhanced Ad-mediated cytotoxicity and accelerated cell death.
  • Intratumoral coinjection of Ad and AAV improved antitumor activity and mouse survival in xenograft models.

Conclusions:

  • Accidental or intentional AAV coinfection significantly impacts Ad propagation and efficacy.
  • AAV coinfection enhances the therapeutic potential of Ad-mediated virotherapy by increasing cytotoxicity and improving antitumor outcomes.

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